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Clinical Crossroads | Clinician's Corner

A 52-Year-Old Woman With Disabling Peripheral Neuropathy:  Review of Diabetic Polyneuropathy

Seward B. Rutkove, MD, Discussant
JAMA. 2009;302(13):1451-1458. doi:10.1001/jama.2009.1377.
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Ms Q is a 52-year-old woman who has had progressive polyneuropathy in the setting of diabetes for the past 8 years. Ms Q's major disability is that of increasingly severe neuropathic pain and cramps that have been poorly responsive to a variety of therapies, including gabapentin and topiramate. The diagnosis of and differential diagnosis for diabetic polyneuropathy are reviewed herein. In general, treatment options for diabetic polyneuropathy remain primarily symptomatic. Improving the metabolic profile through weight loss, exercise, and if necessary, medications may help slow neuropathy progression. Many medications are effective in reducing pain, and newly developed ones, such as pregabalin and duloxetine, while specifically marketed for diabetic neuropathy, are likely to be no better and are considerably more expensive than older ones. α-Lipoic acid appears to be effective as well.

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A 58-Year-Old Woman With Disabling Peripheral Neuropathy
Posted on October 2, 2009
Zhu Shen, MD, PhD
Southwest Hospital, Third Military Medical University
Conflict of Interest: None Declared
Epidemiology Neuropathy is a common complication of diabetes. It increases with both age and duration of diabetes. The overall prevalence of neuropathy was estimated 28.5%, from 5% in the 20-29 year age group to 44.2% in the 70-79 group (1). The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long- standing disease (2).
Who should be tested and how? There is increasing evidence that even pre-diabetic conditions are also associated with some forms of neuropathy (3). Thus people with diabetes, regardless of the presence of symptoms and/or signs of peripheral nerve dysfunction, should be tested periodically. The evaluation requires a careful history and clinical examination of the feet, including patient questionnaire. Nerve conduction studies can quantify the degree of nerve injury and neuropathy progression over a long period of time, particularly if the patient is asymptomatic. Because there are no distinguishing features unique to diabetic neuropathy, other possible causes of neuropathic disorders must be ruled out by careful history, physical examination and imaging examinations (2).
Treatment options Recent progress has been made toward understanding the biochemical mechanisms of diabetic neuropathy, and as a result, new treatment modalities are being explored. Treatment options include pharmacological and nonpharmacological treatments. The former include glycemic control, symptomatic therapies (such as antidepressants, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, mexilitine, opiates, and so on), causal therapies (such as ranirestat, zenarestat, benfotiamine, alpha-lipoic acid, and so on) (2). Despite these choices, diabetic neuropathy continues to pose considerable challenge to clinicians. Many therapies are available to alleviate the symptoms of diabetic neuropathy, but few options are available to eliminate the root causes. Based on efficacy and safety data benfotiamine and alpha-lipoic acid should be considered as first choices among pathogenically-oriented treatments. Most likely, combination therapy will be applied in the future for neuropathy treatment. The optimal choice could be to combine pathogenically-oriented and symptomatic treatment (4, 5).
Lack of promising responses and unwanted adverse effects of conventional drug treatments force many patients to try alternative therapies such as acupuncture and near-infrared phototherapy (6). Nonpharmacological treatment also includes stem cell transplantation. Recent evidence suggested that diabetic neuropathy is causally related to impaired angiogenesis and deficient growth factors. Evidence showed that bone marrow-derived endothelial progenitor cells could reverse various manifestations of diabetic neuropathy in rats. These therapeutic effects were mediated by direct augmentation of neovascularization in peripheral nerves (7, 8). These findings suggest that EPC transplantation could represent an innovative therapeutic option. Treatment of diabetic foot by autologous transplantation of bone-marrow cells was demonstrated in a randomized trial in 2002 (9).
Recommendations Two recommendations: Firstly, general consensus holds that good glucose control should be the first step in the treatment of any form of diabetic neuropathy. Secondly, combination therapy should be applied and the optimal choice should be to combine symptomatic and pathogenetically oriented treatment, including the promising stem cell transplantation.
No relevant financial interests.
REFERENCES
1. Young MJ, Boulton AJ, MacLeod AF, et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993; 36: 150-154.
2. Edwards JL, Vincent AM, Cheng HT, et al. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008; 120: 1-34.
3. Singleton JR, Smith AG, Russell JW, et al. Microvascular complications of impaired glucose tolerance. Diabetes. 2003; 52: 2867-2873.
4. Várkonyi T, Kempler P. Diabetic neuropathy: new strategies for treatment. Diabetes Obes Metab. 2008; 10: 99-108.
5. Burekoviæ A, Terziæ M, Alajbegoviæ S, et al. The role of alpha-lipoic acid in diabetic polyneuropathy treatment. Bosn J Basic Med Sci. 2008; 8: 341-345.
6. Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care. 2009; 3: 136-143.
7. Jeong JO, Kim MO, Kim H, et al. Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation. 2009; 119: 699-708.
8. Shibata T, Naruse K, Kamiya H, et al. Transplantation of bone marrow- derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes. 2008; 57: 3099-3107.
9. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002; 360: 427-435.
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